• Safety/Efficacy
• Frequency of severe adverse events in each arm. Hypothesis based upon NIH data was a rate of 6% severe adverse event with methotrexate compared to 30% with azathioprine (24% in one study on RA and 46% in one study on Sjögren syndrome).
• Evaluation was planned after the last included patient has completed the assigned trial regimen (after 12 months of maintenance regimen or because of drug withdrawal).

• Relapse-free survival rate.
• Cumulative event-free survival rate (adverse event- and relapse-free survival rate).
• Health quality assessment using HAQ and SF36.
• Efficacy of induction therapy with pulsed cyclophosphamide.
• Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen.

Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.

• Drug: Azathioprine: 2 mg/kg/day
• Drug: methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week

Inclusion Criteria:

• Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
• microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria > 1 g/day, renal insufficiency defined as a serum creatininemia > 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).

Exclusion Criteria:

• MPA patients with no poor prognosis factor;
• localized WG;
• relapse of previously known WG or MPA;
• treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
• co-existence of another multi-system autoimmune disease;
• malignancy (unless considered in complete remission and with no therapy for at least 3 years);
• contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women;
• infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.